The polyene macrolide natural product amphotericin B (AmB) is the archetype for both small molecules that form ion channels in living cells1 and antibiotics that are inherently refractory to microbial resistance.2 AmB is also, unfortunately, highly toxic,3 which often limits its effective utilization as the last line of defense against life-threatening systemic fungal infections. Because both the incidence of such fungal infections and resistance to all other classes of antifungals are on the rise,2 finding a way to improve the therapeutic index of AmB has become an increasingly important problem. Some progress has been made with liposomal formulations, but they are often prohibitively expensive,4 and substantial toxicity still remains.5 Despite 50 years of extensive efforts worldwide, a clinically viable derivative of AmB with an improved therapeutic index has yet to emerge.6 